ENDS Toxicity / Carcinogenic

Studies, Surveys, Papers, and Case Studies

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  • Topic
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  • Year (list new to old) Name of Study (In link format to the study)
  • Brief Summary
  • Link to PDF Version
  • Citation
  • Acknowledgements (funded by, helped by)
  • Keywords
  • Other

ENDS vs Smoking Tobacco, Heated Tobacco Product/Heat not Burn, or Nicotine Replacement Therapy

2020 Comparison of the chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells

• We first report that HTP (Heated Tobacco Product) delivers slightly less nicotine and emits much lower amounts of carbonyl and PAH compounds than tobacco cigarettes.
• However, HTP emissions still contain carcinogenic compounds (e.g. formaldehyde, acetaldehyde and benzo[a]pyrene) and the amounts of carbonyls and PAHs in HTP aerosols are higher than in e-cig vapours.
• In accordance with the levels of toxic compounds in each aerosol, HTP aerosol exhibits reduced cytotoxicity compared to cigarette smoke but higher than e-cig vapours (vapors).
• HTP and e-cig have the potential to increase oxidative stress and inflammatory response, in a manner very similar to that of cigarette smoke, but only after a more intensive exposure. In addition, our data support that e-cig use at higher power settings emit higher carbonyl and PAH compounds and, consequently, generate more oxidative stress.
• Finally, this study contributes to a better understanding of HTP and e-cig emission properties and their related toxicological impacts and provides important data needed for risk assessment purposes, by demonstrating that HTP might be less harmful than tobacco cigarettes but considerably more harmful than e-cig.
• PDF Version
• Citation: Dusautoir R, Zarcone G, Verriele M, Garc¸on G, Fronval I, Beauval N, Allorge D, Riffault V, Locoge N, Lo-Guidice J-Marc, Antherieu S, Comparison of the ´ chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells, Journal of Hazardous Materials (2020), doi: 10.1016/j.jhazmat.2020.123417
• Acknowledgement: This work was supported by the French Institute of Cancer (INCa) and the French Institute for Public Health Research (IResP): Contracts n°INCa_11505 and n°INCa_13648.

2020 Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System

• The results of this study concorded with evidence that complete switching from combustible cigarettes to vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases.
• PDF Version
• Citation: Joanna Jay, BA, Erika L Pfaunmiller, PhD, Norman J Huang, PhD, Gal Cohen, PhD, Donald W Graff, PharmD, Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System, Nicotine & Tobacco Research, Volume 22, Issue 8, August 2020, Pages 1285–1293, doi:10.1093/ntr/ntz206
• Acknowledgements: JJ, NJH, GC, and DWG are employees of JUUL Labs, Inc. ELP is an employee of Frontage Labs. ELP and DWG were employed by Celerion Inc. at the time the study was conducted. Celerion is a contract research organization that performs studies on tobacco and nicotine-containing products, sponsored by the pharmaceutical and tobacco industries.
• Keywords: nicotine, smoking, adult, biological markers, tobacco, urine, cigarettes, smokers

ENDS (without comparison to other products)

2018 Metal emissions from e-cigarettes: a risk assessment analysis of a recently-published study

• EC emissions contain trace levels of metals. For almost all metals, unrealistically high levels of liquid need to be consumed in order for total daily exposure to exceed established limits.
• PDF Version
• Citation: : Konstantinos E. Farsalinos & Brad Rodu (2018): Metal emissions from ecigarettes: a risk assessment analysis of a recently-published study, Inhalation Toxicology, DOI: 10.1080/08958378.2018.1523262
• Acknowledgements: In the past 36 months, two studies by KF were performed using unrestricted funds from the nonprofit association AEMSA and one study by the nonprofit association Tennessee Smoke-Free Association. BR is supported by unrestricted grants from tobacco manufacturers to the University of Louisville and by the Kentucky Research Challenge Trust Fund.
• KEYWORDS: E-cigarettes; aerosol; metals; risk assessment

2016 Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols

• Most potential impurities or degradation products were not detectable.
• Impurities or degradation products found were below occupational exposure limits
• Citation: Jason W. Flora, Naren Meruva, Chorng B. Huang, Celeste T. Wilkinson, Regina Ballentine, Donna C. Smith, Michael S. Werley, Willie J. McKinney, Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols, Regulatory Toxicology and Pharmacology, Volume 74, 2016, Pages 1-11, ISSN 0273-2300, doi: 10.1016/j.yrtph.2015.11.009.
• Keywords, E-cigarettes, E-vapor, Harmful and potentially harmful constituents (HPHC), Formulation, Aerosol

2014 Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks

• Threshold Limit Values (TLVs), were conducted under “worst case” assumptions about both chemical content of aerosol and liquids as well as behavior of vapers.
• There was no evidence of potential for exposures of e-cigarette users to contaminants that are associated with risk to health at a level that would warrant attention if it were an involuntary workplace exposures.
• Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces. However, the aerosol generated during vaping as a whole (contaminants plus declared ingredients) creates personal exposures that would justify surveillance of health among exposed persons in conjunction with investigation of means to keep any adverse health effects as low as reasonably achievable.
• Exposures of bystanders are likely to be orders of magnitude less, and thus pose no apparent concern.
• PDF Version
• Burstyn, I. Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks. BMC Public Health 14, 18 (2014). doi: 10.1186/1471-2458-14-18
• Acknowledgements: Funding for this work was provided by The Consumer Advocates for Smoke-free Alternatives Association (CASAA) Research Fund. CASAA is an all-volunteer, donation-funded, non-profit organization devoted to defending consumer access to and promoting tobacco harm reduction; it is a consumer (not industry) advocacy NGO. For more information, see http://casaa.org/. CASAA exercised no editorial control over the author’s writing or analysis: the author, not the funder, had full control of the content.
• Keywords: Vaping, e-cigarettes, Tobacco harm reduction, Risk assessment, Aerosol, Occupational exposure limit

2013 Electronic Cigarettes: A Short Review

• From our review of the literature and bearing in mind the long experience with theatrical mists, the short-term toxicity can be considered to be very low
• Many smokers see the e-cigarette as a good way to quit smoking
• PDF Version
• Citation: J.F. Bertholon, M.H. Becquemin, Annesi-Maesano, B. Dautzenberg, Respiration 2013;86:433–438, Electronic Cigarettes: A Short Review, DOI: 10.1159/000353253
• Key Words: Electronic cigarettes, Propylene glycol, Nicotine

Flavoring in ENDS Products (Flavour)

2019 High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate

• Our results clearly show a lower toxicity of e-liquids, including flavoured e-liquids, when compared to CSC (cigarette smoke condensate). Typically, more than 100 times higher concentrations of CFs (Base liquids, with or without nicotine, and commercial, flavoured, nicotine-containing e-liquids) are required to elicit the same response as those observed for 3R4F CSC in specific endpoints.
• Flavours play a critical role in attracting, and retaining smokers to e-cigarettes.
• PDF Version
• Citation: Lukasz Czekala, Liam Simms, Matthew Stevenson, Edgar Trelles-Sticken, Paul Walker, Tanvir Walele, High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate, Toxicology in Vitro, Volume 58, 2019, Pages 86-96, ISSN 0887-2333, doi:10.1016/j.tiv.2019.03.018.
• Acknowledgements: This work was funded and supported by Fontem Ventures B.V., part of Imperial Brands Group PLC.
• Keywords: Flavours, In vitro, Normal Human Bronchial Epithelial cells, High Content Screening, E-liquids, Cigarette

2019 Toxicity classification of e-cigarette flavouring compounds based on European Union regulation: analysis of findings from a recent study

• The vast majority of flavouring (flavoring) compounds in e-cigarette liquids as reported in a recent study were present at levels far lower than needed to classify them as toxic.
• PDF Version
• Farsalinos, K., Lagoumintzis, G. Toxicity classification of e-cigarette flavouring compounds based on European Union regulation: analysis of findings from a recent study. Harm Reduct J 16, 48 (2019). doi: 10.1186/s12954-019-0318-2
• Acknowledgements: The authors report no conflict of interest for the past 36 months. For the past 60 months, KF has published 2 studies funded by the non-profit association AEMSA and 1 study funded by the non-profit association Tennessee Smoke-Free Association.

2018 Do flavouring compounds contribute to aldehyde emissions in e-cigarettes?

• Aldehyde emissions from all flavoured liquids were 79–99.8% lower than smoking and lower than commonly measured indoor levels and occupational and indoor safety limits.
• PDF Version
• Citation: Konstantinos E. Farsalinos, Vassilis Voudris, Do flavouring compounds contribute to aldehyde emissions in e-cigarettes?, Food and Chemical Toxicology, volume 115, 2018, Pages 212-217, ISSN 0278-6915, doi:10.1016/j.fct.2018.02.059.
• Acknowledgements: The study was funded by Public Health England.

2015 An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids

• Individual flavours or groups of flavours were added to the tobacco rod and the resultant smoke was analysed for priority smoke constituents and tested in several in vitro tests as well as 90-day rat inhalation studies. In general, addition of the flavours had no effect on, or reduced the levels of most of the measured smoke constituents.”
• PDF Version
• Citation: S. Costigan, C. Meredith, An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids, Regulatory Toxicology and Pharmacology, Volume 72, Issue 2, 2015, Pages 361-369, ISSN 0273-2300, doi: 10.1016/j.yrtph.2015.05.018.
• Acknowledgements: This work was joint funded by Nicoventures and British American Tobacco (BAT), and the authors are full time employees of Nicoventures and British American Tobacco (BAT).

Other ENDS Liquids Ingredients (PG/VG/Nicotine)

2020 Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014)

• Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was

1. highest for smokeless tobacco users (993.3 ng/g creatinine),
2. followed by all types of combustible tobacco product users (285.4 ng/g creatinine),
3. poly tobacco users (278.6 ng/g creatinine),
4. and e-cigarette (ENDS) product users (6.3 ng/g creatinine).

• PDF Version
• Citation: Baoyun Xia, PhD, Benjamin C Blount, PhD, Tonya Guillot, MPH, Christina Brosius, MPH, Yao Li, BS, Dana M Van Bemmel, PhD MPH, Heather L Kimmel, PhD, Cindy M Chang, PhD MPH, Nicolette Borek, PhD, Kathryn C Edwards, PhD, Charlie Lawrence, PhD, Andrew Hyland, PhD, Maciej L Goniewicz, PhD PharmD, Brittany N Pine, BS, Yang Xia, PhD, John T Bernert, B Rey De Castro, ScD, John Lee, BS, Justin L Brown, MPH, Stephen Arnstein, MS, Diane Choi, BS, Erin L Wade, BS, Dorothy Hatsukami, PhD, Gladys Ervies, PhD, Angel Cobos, BS, Keegan Nicodemus, BS, Dana Freeman, BS, Stephen S Hecht, PhD, Kevin Conway, PhD, Lanqing Wang, PhD, Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014), Nicotine & Tobacco Research, , ntaa110:10.1093/ntr/ntaa110
• Acknowledgements: This manuscript is supported with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, and the Center for Tobacco Products, Food and Drug Administration, Department of Health and Human Services, under contract to Westat (contract nos. HHSN271201100027C and HHSN271201600001C) and through an interagency agreement between the FDA Center for Tobacco Products and the Centers for Disease Control and Prevention.
• Keywords: creatinine, exposure, biological markers, nitrosamines, tobacco, urinary tract, electronic cigarettes, ENDS

2017 Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints

• Animal Study
• Standard toxicological endpoints were complemented with systems toxicological analyses using transcriptomics, proteomics, and lipidomics of lung tissue, liver tissue, and serum. Both standard and systems toxicology endpoints demonstrated very limited biological effects of PG/VG aerosol with no signs of toxicity Systems toxicology analyses detected biological effects of nicotine exposure, which included up-regulation of the xenobiotic-metabolizing enzymes Cyp1a1 and Fmo3 in the lung and metabolic effects, likely interlinked with a generalized stress response to nicotine present in the exposure aerosols
• PDF Version
• Citation: Blaine Phillips, Bjoern Titz, Ulrike Kogel, Danilal Sharma, Patrice Leroy, Yang Xiang, Grégory Vuillaume, Stefan Lebrun, Davide Sciuscio, Jenny Ho, Catherine Nury, Emmanuel Guedj, Ashraf Elamin, Marco Esposito, Subash Krishnan, Walter K. Schlage, Emilija Veljkovic, Nikolai V. Ivanov, Florian Martin, Manuel C. Peitsch, Julia Hoeng, Patrick Vanscheeuwijck, Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints, Food and Chemical Toxicology, Volume 109, Part 1, 2017, Pages 315-332, ISSN 0278-6915, doi:10.1016/j.fct.2017.09.001.
• Acknowledgements: The work reported in this publication was funded solely by Philip Morris International (PMI). All authors are (or were) employees of PMI R&D or worked for PMI R&D under contractual agreements.

2017 A Review on the Safety of Inhalation of Propylene Glycol in E-cigarettes

• Tests performed by the FDA have shown that e-cigarettes have similar nicotine levels and trace contaminants as NRT products.
• Propylene glycol (PG) is generally recognized as safe by oral, dermal or inhalation routes and has been a common ingredient in all American made tobacco cigarettes for seven decades.”
• PDF Version
• Citation: A Review on the Safety of Inhalation of Propylene Glycol in E-cigarettes, Karyn I. Cotta}, 2017

2014 Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks

• Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces
• PDF Version
• Burstyn, I. Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks. BMC Public Health 14, 18 (2014). doi: 10.1186/1471-2458-14-18
• Acknowledgements: Funding for this work was provided by The Consumer Advocates for Smoke-free Alternatives Association (CASAA) Research Fund. CASAA is an all-volunteer, donation-funded, non-profit organization devoted to defending consumer access to and promoting tobacco harm reduction; it is a consumer (not industry) advocacy NGO. For more information, see http://casaa.org/. CASAA exercised no editorial control over the author’s writing or analysis: the author, not the funder, had full control of the content.
• Keywords: Vaping, e-cigarettes, Tobacco harm reduction, Risk assessment, Aerosol, Occupational exposure limit

2013 Analysis of refill liquids for electronic cigarettes

• The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in some brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm.
• PDF Version
• Citation: Etter, J.‐F., Zäther, E. and Svensson, S. (2013), E‐liquids. Addiction, 108: 1671-1679. doi: 10.1111/add.12235

2006 Reregistration Eligibility Decision (RED) for propylene glycol and dipropylene glycol (PDF Version)

• Upon reviewing the available toxicity information, the Agency has concluded that there are no endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol. This conclusion is based on the results of toxicity testing of propylene glycol in which dose levels near or above testing limits (as established in the OPPTS 870 series harmonized test guidelines) were employed in experimental animal studies and no significant toxicity observed.
• A review of the available data has shown propylene glycol to be negative for carcinogenicity in studies conducted up to the testing limit doses established by the Agency; therefore, no further carcinogenic analysis is required.

More Information

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